The medical need to design immediate release analgesics has been a continuous goal and challenge to the pharmaceutical industry. For example, ibuprofen, a powerful anti-inflammatory, analgesic, and antipyretic agent, has been formulated into different immediate release dosage forms such as tablets, capsules, effervescent granules, and solutions. However, the poor aqueous solubility and the very bitter taste of ibuprofen have limited formulation options.
Available techniques to manufacture immediate release oral ibuprofen pharmaceuticals can be classified into two major categories. The first category of techniques includes various solvent systems to prepare ibuprofen solutions that can be used as bulk liquids or can be filled into hard or soft capsules. A typical example of the solvent systems technique is described in U.S. Pat. No. 4,690,823 (Lohner et al.), where ibuprofen solutions are prepared with the aid of a polyoxyethylene-polyoxypropylene polymer or in a mixture of a polyalkylene glycol and a surfactant, such as polyoxyethylene-(40)-glycerol trihydroxystearate polyoxyethylene-(20)-stearyl alcohol or polyoxyethylene-(20)-sorbitan monostearate.
Other examples of the solvent systems technique are described in U.S. Pat. No. 5,071,643 (Yu et al.) and U.S. Pat. No. 5,376,688 (Morton et al.). The solvent systems consist of polyethylene glycol or other polymers such as diethylene glycol monoethyl ether, polyglycerol oleate, and mixtures thereof, containing 0.2 to 1.0 mole equivalents of a strong base consisting of the hydroxide form per mole of ibuprofen. The solvent systems additionally use ionizing agents, such as potassium hydroxide, sodium hydroxide, and ammonium hydroxide.
Other solvent systems are described in U.S. Pat. No. 5,468,502 (Argiriadi et al.), where surfactants and ammonium acetate are used to dissolve ibuprofen.
While the above examples of oral ibuprofen products can contain up to 67% w/w ibuprofen, they are mainly for capsule filling, and cannot be used directly for bulk oral solutions because of their unpleasant taste. In addition, the use of ionizing agents usually requires long period of time, vigorous mixing, and/or application of heat, due to the slow ionization in the non-aqueous media used.
U.S. Pat. No. 4,861,797 (Hass) has described a solvent system for ibuprofen where a clear and palatable liquid solution is made in an aqueous medium containing bicarbonate and methylcellulose. However, the ibuprofen solutions only contain a maximum ibuprofen concentration of only 8%.
The second category of techniques for manufacturing immediate release oral ibuprofen products is based on solid powders or granules that can be filled in two piece capsules or compressed into tablets. For this technique, binders are always required to increase powder density and enlarge particle size. Since binders usually act against immediate drug release, low molecular weight water soluble polymeric binders are often used. U.S. Pat. No. 6,596,312 (Erkoboni et al.) describes the use of hydrolyzed polysaccharide (i.e., cellulose hydrolyzate) as a binder for immediate release tablets. Similarly, U.S. Pat. No. 5,080,907 (Iijima et al.) describes the use of hydrolyzed proteins such as gelatin hydrolyzate for tablets and dry powder for suspension. Such powders or granules use relatively high amounts of the polymeric binders, which results in low drug concentrations.
In view of the foregoing limitations, there remains a need for oral ibuprofen products with higher drug concentrations, as well as methods of manufacturing the oral ibuprofen products. The invention provides such oral ibuprofen products, as well as production methods thereof.